Gliomas are the most common primary malignant brain tumors in adults and are often highly fatal. Little is known about the etiology of these tumors. Recent studies suggest that individuals with allergies may have a lower risk of glioma. Studies have also reported associations with detoxification genes, especially GSTT1 and GSTP1. However, most epidemiologic studies reporting these associations have been case- control studies, which are particularly prone to biases, given the high fatality of gliomas. To examine hypotheses related to allergies and genetic susceptibility, we propose to draw on five established prospective cohorts: the Health Professionals Follow-Up study, the Nurses'Health Study I, the Nurses'Health Study II, the Physicians'Health Study, and the Women's Health Study. Specifically, we propose to examine IgE levels (total, food and respiratory specific) in blood specimens, SNPs (both alleles and haplotypes) of genes strongly related to allergies or asthma (IL-4, IL-4Ralpha, IL-13, FceRI-p, IL-10, CTLA- 4), and known functional variants of two detoxification genes (GSTP1 and GSTT1) in relation to the risk of gliomas. In these five cohorts, blood samples were collected from participants prior to disease diagnosis. For the genetic polymorphism analyses, we will have 341 incident glioma cases with 3 matched controls, using a nested case-control design. In addition, we propose to obtain tissue blocks from all incident glioma cases to classify the different types of gliomas using molecular markers (TP53 mutations, EGFR amplification, chromosome loss of 1p and 10p). Use of molecular markers to identify subtypes of gliomas may enhance our ability to uncover etiologic risk factors. This will be the largest prospective study of gliomas to date, and with its considerable strengths, holds the promise of contributing substantially to our understanding of the relation between allergies, genetic susceptibility and adult glioma risk. Improving our understanding of the etiology of gliomas will provide opportunities for treatment options or prevention of this deadly cancer.